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The thioredoxin system in cancer
Elias S J Arnér1, Arne Holmgren
1Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden. elias.arner@ki.se
Seminars in Cancer Biology
|November 10, 2006
Summary
The thioredoxin system (thioredoxin, NADPH, and thioredoxin reductase) is vital for cellular redox balance and has roles in cancer. Both thioredoxin and thioredoxin reductase are promising chemotherapy targets.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- The thioredoxin system, comprising thioredoxin (Trx), NADPH, and thioredoxin reductase (TrxR), is fundamental to cellular redox homeostasis.
- This system regulates critical cellular processes including growth, apoptosis, and defense against oxidative stress.
- Dysregulation of the thioredoxin system is implicated in various mammalian cell functions and diseases, notably cancer.
Purpose of the Study:
- To explore the multifaceted roles of the thioredoxin system in mammalian cells.
- To investigate the implications of thioredoxin and thioredoxin reductase in cancer development and progression.
- To evaluate the potential of the thioredoxin system as a therapeutic target in cancer treatment.
Main Methods:
- Review and synthesis of existing scientific literature on the thioredoxin system.
- Analysis of studies investigating thioredoxin and thioredoxin reductase expression in tumors.
- Examination of data linking thioredoxin system components to cellular processes like DNA synthesis, immune function, and apoptosis.
Main Results:
- Reduced thioredoxin activates transcription factors and aids antioxidant defense by repairing damaged proteins and donating electrons to peroxiredoxins.
- The thioredoxin system is essential for deoxyribonucleotide synthesis, crucial for DNA replication and repair.
- Thioredoxin reductase, a selenoenzyme, plays roles in selenium metabolism and has been linked to cancer chemoprevention and the carcinogenic process.
Conclusions:
- The thioredoxin system is integral to cellular health and has diverse roles in cancer, including potential links to chemotherapy resistance and tumor invasiveness.
- Elevated levels of thioredoxin and thioredoxin reductase are observed in some tumors, suggesting their involvement in tumorigenesis.
- Both thioredoxin and thioredoxin reductase represent significant and promising targets for novel chemotherapeutic strategies against cancer.
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